Stroke and traumatic brain injury often involve the cerebral cortex and are leading causes of functional disability collectively affecting greater than 2 million people per year in the United States. The negative personal, social and economic impacts of these disorders are staggering. In clinical practice, variable levels of motor recovery are commonly observed and occur following damage of the motor cortex or its descending pathways. Although there appears to be considerable functional plasticity in the adult brain, the mechanisms underlying motor recovery following subtotal brain injury remain poorly understood. Our major goal is to test the hypothesis that a central mechanism of functional recovery of arm movement occurs through reorganization of the corticospinal projection from intact frontal motor areas located ipsilateral to a subtotal brain lesion and that forced use therapy enhances the corticospinal linkage. At clinically significant time intervals and under different durations of forced use therapy, we will test this hypothesis by studying neuroplastic adaptations of the corticospinal projection from the arm area of the supplementary motor cortex (M2) following isolated resection of the ipsilateral arm areas of: a) the primary motor cortex (M1) + the dorsolateral premotor cortex (LPMCd) and; b) M1 + LPMCd + the primary somatosensory cortex (S1). Both of these lesion categories involve part of the motor cortex that is typically involved in the most common form of human stroke, namely middle cerebral artery infarction. Hand recovery will be tracked by analyzing 3-D hand and digit motion during reaching and grasping, force control during grasping and lifting, and bimanual coordination using 3 specialized testing methods. This project will lead to a greater understanding of the role of the frontal motor cortices in the recovery process of arm movement following cortical injury and will determine the effect that short and long-term forced use therapy has on recovery outcome and its accompanying neuroplastic response. This research will also assess whether the integrity of spared corticospinal projections from intact motor areas positioned ipsilateral to a lesion of the cerebral cortex underlie functional restitution of hand movement control and whether long-term reorganization of intact corticospinal terminals accompany the recruitment of parallel cortical motor areas after subtotal brain injury. This information will assist in establishing predictors to identify a large patient population that may recover favorably after brain injury with appropriate therapy. Furthermore, it will assist in guiding creative rehabilitative interventions aimed at enhancing frontal cortical participation in the recovery process. PUBLIC HEALTH RELEVANCE: Stroke and traumatic brain injury often involve the cerebral cortex and are leading causes of functional disability collectively affecting greater than 2 million people a year in the United States. This project will lead to a greater understanding of the role of the frontal motor cortices in the recovery process of arm movement following cortical injury and will determine the effect that short and long-term forced use therapy has on recovery outcome and its accompanying neuroplastic response. This information will assist in establishing predictors to identify a large patient population that may develop favorably after brain injury and will assist in guiding creative rehabilitative interventions aimed at enhancing frontal cortical participation in the recovery process.